Donor Enhancement With Plerixafor Post Myeloablative Allogeneic Transplant
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 4/21/2016 |
| Start Date: | December 2011 |
| End Date: | February 2018 |
A Phase I/II Study: Enhancing Donor Hematopoietic Cell Engraftment With Plerixafor in Myeloablative Allogeneic Hematopoietic Cell Transplantation
This phase I/II clinical trial will test the safety and the efficacy of post transplant
administration of plerixafor in enhancing hematological recovery in humans. Patients who are
appropriate candidates for myeloablative allogeneic stem cell transplantation from an
HLA-matched sibling, matched unrelated donor or umbilical cord blood are eligible for
enrollment. The investigators plan to enroll a total of 50 patients for this study (30
patients with HLA-matched sibling or matched unrelated donor transplant, and 20 patients
with umbilical cord blood transplant). During phase I study, a small number of patients (3-6
patients from each group) will be enrolled to determine the safety of post transplant
administration of plerixafor. Patients will receive plerixafor given at 240 µg/kg
subcutaneously every other day beginning at day +2 after transplant until day +21 or
engraftment. Limiting toxicities are defined as primary or secondary graft failure,
plerixafor-related severe premature ventricular arrhythmia or death. If safety criteria are
met from the investigators phase I study, the investigators will proceed with phase II study
to determine the efficacy of post transplant administration of plerixafor in enhancing
haematological recovery. The experimental aspect of this study is the use of plerixafor and
all other aspects of care will be in line with the standard of care. Both Phase I and Phase
II patients will be combined for efficacy analysis, and data collected from this study will
be compared with the investigators historical control. The results from this study will set
the stage and provide the justification for a larger phase 3 trial.
administration of plerixafor in enhancing hematological recovery in humans. Patients who are
appropriate candidates for myeloablative allogeneic stem cell transplantation from an
HLA-matched sibling, matched unrelated donor or umbilical cord blood are eligible for
enrollment. The investigators plan to enroll a total of 50 patients for this study (30
patients with HLA-matched sibling or matched unrelated donor transplant, and 20 patients
with umbilical cord blood transplant). During phase I study, a small number of patients (3-6
patients from each group) will be enrolled to determine the safety of post transplant
administration of plerixafor. Patients will receive plerixafor given at 240 µg/kg
subcutaneously every other day beginning at day +2 after transplant until day +21 or
engraftment. Limiting toxicities are defined as primary or secondary graft failure,
plerixafor-related severe premature ventricular arrhythmia or death. If safety criteria are
met from the investigators phase I study, the investigators will proceed with phase II study
to determine the efficacy of post transplant administration of plerixafor in enhancing
haematological recovery. The experimental aspect of this study is the use of plerixafor and
all other aspects of care will be in line with the standard of care. Both Phase I and Phase
II patients will be combined for efficacy analysis, and data collected from this study will
be compared with the investigators historical control. The results from this study will set
the stage and provide the justification for a larger phase 3 trial.
Recruitment to this trial will be stratified by donor type as HLA matched sibling, matched
unrelated donor or umbilical cord blood. Patients will be conditioned with a myeloablative
regimen such as, but not limited to, total body irradiation and cyclophosphamide. The donor
stem cell grafts will come from mobilized peripheral blood of 8/8 or 7/8 HLA-identical
family members, 8/8 (HLA A, B, C, DRBeta1) allele-level matched unrelated donors, or dual
umbilical cord blood grafts with at least 4 of 6 HLA matching at HLA A and B (low
resolution) and DRBeta1 (at high resolution). The target CD34+ cell dose will be 5 X
10(6)/kg recipient ideal body weight. For HLA matched sibling or matched unrelated donor
(MUD) transplants, all patients will receive a minimum of 2 X 10(6) CD 24+ cells/kg. For
cord blood transplants, each unit will contain a minimum total nucleated cell count of of
1.5 X 10(7)/kg. Post-transplant GVHD prophylaxis will be given per institutional standard.
unrelated donor or umbilical cord blood. Patients will be conditioned with a myeloablative
regimen such as, but not limited to, total body irradiation and cyclophosphamide. The donor
stem cell grafts will come from mobilized peripheral blood of 8/8 or 7/8 HLA-identical
family members, 8/8 (HLA A, B, C, DRBeta1) allele-level matched unrelated donors, or dual
umbilical cord blood grafts with at least 4 of 6 HLA matching at HLA A and B (low
resolution) and DRBeta1 (at high resolution). The target CD34+ cell dose will be 5 X
10(6)/kg recipient ideal body weight. For HLA matched sibling or matched unrelated donor
(MUD) transplants, all patients will receive a minimum of 2 X 10(6) CD 24+ cells/kg. For
cord blood transplants, each unit will contain a minimum total nucleated cell count of of
1.5 X 10(7)/kg. Post-transplant GVHD prophylaxis will be given per institutional standard.
Inclusion Criteria:
- Age 18 to 65 years.
- 8/8 or 7/8 HLA-identical matched sibling OR Allele level 8/8 (HLA-A, B, C, DR
Beta1)matched unrelated donor or 4/6 or better HLA matched cord blood.
- Patients with high risk hematologic malignancies who are appropriate candidates for a
myeloablative allogeneic stem cell transplantation.
- Patients with a history of CNS disease must have been treated and have no active CNS
disease at the time of protocol treatment.
- ECOG performance status < or equal to 2
- Patients must have adequate function of other organ systems as measured by:
- Creatinine clearance (by Cockcroft Gault equation) > or equal to 30ml/min. Hepatic
transaminases (ALT/AST) < or equal to 4 x normal, bilirubin < or equal to 2.0 mg/dl.
- Pulmonary function tests demonstrating FVC and FEV1 of > or equal to 50% of predicted
for age and DLCO > or equal to 50% of predicted.
- Ejection fraction of > or equal to 45% by echocardiogram, radionuclide scan or
cardiac MRI.
- Patients must be HIV negative.
- Patients must not be pregnant.
Exclusion Criteria:
- Patients with > 5% blasts in bone marrow or peripheral circulation.
- Uncontrolled infection.
- Class III or IV angina as per NYHA criteria.
We found this trial at
2
sites
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
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171 Ashley Avenue
Charleston, South Carolina 29425
Charleston, South Carolina 29425
843-792-1414
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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